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ID PMID Title PublicationDate abstract
11039782 Gene therapy approaches for treating rheumatoid arthritis. 2000 Oct Current gene therapy approaches for treating rheumatoid arthritis have made use of gene transfer technology as an improved delivery system for emerging proteins and other biologicals whose activities may have therapeutic value. Preclinical research has focused on two primary directions, evaluation of methods of gene delivery and identification of gene products with antiarthritic potential. Although there are reports involving systemic gene delivery, the bulk of effort has focused on local, intraarticular administration using ex vivo and in vivo methods. Viral-based vectors, including adenovirus, adeno-associated virus and herpes simplex virus have the greatest efficiency of gene delivery after intraarticular injection and are capable of generating relevant levels of gene products in several animal models of disease. However, there are limitations to existing generations of these systems that currently preclude their clinical application. Those gene products found to be efficacious in animal models of rheumatoid arthritis include proteins that specifically block the activity of the primary inflammatory cytokines, and include interleukin-1 receptor antagonist and soluble receptors for tumor necrosis factor and interleukin-1. Delivery and expression of genes encoding certain cytokines such as interleukins -4, -10, and -13 and viral interleukin-10, that block synthesis of inflammatory mediators and downregulate aspects of cellular and humoral immune pathways have been found beneficial. Although significant progress has been made, leading to Phase I clinical trials, there remain several hurdles to the routine practice of gene therapy for treatment of rheumatoid arthritis.
9697141 [Implant failure after total hip replacement. Comparison of patients with primary coxarthr 1998 Jun The analysis of THR-failures showed that the acetabular component still is the main problem of total hip replacement. The acetabular cup fails more often than the stem. In the midterm analysis the failure rate is a little bit higher in cementless than in cement fixed cups. The known effect that the failure rate of cups fixed with cement increases exponentially 8 to 10 years after implantation, could of course not be seen in this study. The success of the cementless fixation was negatively influenced by the diagnosis rheumatoid arthritis, age over 70 and the fixation manner: the failure rate of threaded cups was higher than the one of press-fit cups although the Zweymüller-cup as well as the Link type V-cup showed good results. The midterm results of the stem were very good for the cementless as for the cemented technique. Some implants showed compared to others significantly worse results. The further implantation should be thought of, what partially has already happened. The results of cementless stem fixation in patients with rheumatoid arthritis, osteoarthrosis and dysplastic osteoarthritis is comparable, so that cementless fixation should be thought of in case of adequate conditions (ability of partial weight bearing for some weeks, age under 60).
11094926 A naturalistic evaluation of cortisol secretion in persons with fibromyalgia and rheumatoi 2000 Feb OBJECTIVE: To compare cortisol levels, diurnal cycles of cortisol, and reactivity of cortisol to psychological stress in fibromyalgia (FM) and rheumatoid arthritis (RA) patients in their natural environment, and to examine the effect on results of accounting for differences among the groups in psychological stress and other lifestyle and psychosocial variables. METHODS: Participants were 21 FM patients, 18 RA patients, and 22 healthy controls. Participants engaged in normal daily activities were signaled with a preprogrammed wristwatch alarm to complete a diary (assessing psychosocial- and lifestyle-related variables) or provide a saliva sample (for cortisol assessment). Participants were signaled to provide 6 diary reports and 6 saliva samples on each of two days. Reports of sleep quality and sleep duration were also made upon awakening. RESULTS: FM and RA patients had higher average cortisol levels than controls; however, there were no differences between the groups in diurnal cycles of cortisol or reactivity to psychological stress. While the groups differed on stress measures, surprisingly, the patient groups reported less stress. Furthermore, statistically accounting for psychosocial- and lifestyle-related differences between the groups did not change the cortisol findings. CONCLUSION: The results provide additional evidence of hypothalamic-pituitary-adrenal axis disturbance in FM and RA patients. While such elevations are consistent with other studies of chronically stressed groups, the elevations in cortisol in this study did not appear to be due to ongoing daily stress, and there was no evidence of disturbed cortisol reactivity to acute stressors.
9667624 Dynamic exercise therapy in rheumatoid arthritis: a systematic review. 1998 Jun The aim of this systematic review was to determine the effectiveness of dynamic exercise therapy in improving joint mobility, muscle strength, aerobic capacity and daily functioning in patients with rheumatoid arthritis (RA). In addition, possible unwanted effects such as an increase in pain, disease activity and radiological progression were studied. A computer-aided search of the MEDLINE, Embase and SCISEARCH databases was performed to identify controlled trials on the effect of exercise therapy. Randomized trials were selected on the effect of dynamic exercise therapy in RA patients with an exercise programme fulfilling the following criteria: (a) intensity level such that heart rates exceeded 60% of maximal heart rate during at least 20 min; (b) exercise frequency > or = 2 a week; and (c) duration of intervention > or = 6 weeks. Two blinded reviewers independently selected eligible studies, rated the methodological quality and extracted data. Six out of 30 identified controlled trials met the inclusion criteria. Four of the six included studies fulfilled > or = 7/10 methodological criteria. Because of heterogeneity in outcome measures, data could not be pooled. The results suggest that dynamic exercise therapy is effective in increasing aerobic capacity and muscle strength. No detrimental effects on disease activity and pain were observed. The effects of dynamic exercise therapy on functional ability and radiological progression are unclear. It is concluded that dynamic exercise therapy has a positive effect on physical capacity. Research on the long-term effect of dynamic exercise therapy on radiological progression and functional ability is needed.
11144291 Soluble HLA-DR antigen levels in serum correlate with rheumatoid arthritis disease activit 2000 Nov We investigated correlations between soluble HLA-DR (sHLA-DR) molecules and several clinical, biological and genetic parameters associated with rheumatoid arthritis (RA) disease activity. Serum sHLA-DR concentrations were determined in 146 samples from 89 RA patients by an ELISA format, using an antibody combination of mouse and rat monoclonal anti-human HLA-DR antibodies. The mean sHLA-DR serum level in RA patients was significantly increased with 277+/-19 ng/ml compared to 142+/-13 ng/ml of 80 healthy controls (P<0.001). In ascending order of significance, correlations were found between serum sHLA-DR and EULAR swelling and pain scores, Waaler-Rose, RA factor, ESR and CRP (P=0.025 to P<0.001). High sHLA-DR levels were defined above 374 ng/ml that was the 95% confidence interval of the controls. Thirty-seven blood samples (25%) in 31 RA patients were above this level. The EULAR pain and swelling scores, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and RA factor were higher (P=0.044 to P<0.001) at the moment of high sHLA-DR concentrations, compared to the lower concentrations. Higher disease activity was further found in groups of RA patients respectively heterozygous or homozygous for the disease-associated epitope (Q)R/KRAA within the HLA-DRB1 chain, compared to the group without this epitope (P<0.017 for part of the results). Likewise, sHLA-DR was respectively 169+/-17 (no disease associated epitope), 324+/-34 (heterozygous) and 442+/-69 ng/ml (homozygous for the disease-associated epitope on HLA-DRB1 alleles) (P<0.017). In conclusion, this study shows significant correlations between serum sHLA-DR levels and RA disease activity parameters, as well as increased sHLA-DR in patients with disease-associated epitope on HLA-DRB1 alleles.
10405930 Gallstones in patients with rheumatoid arthritis. 1999 Jul OBJECTIVE: We performed abdominal ultrasonography (US) on patients with rheumatoid arthritis (RA) to investigate the frequency and characteristics of gallstones (GS). METHODS: Patients with RA (n = 224; 42 male and 182 female) underwent abdominal US. RESULTS: The incidence of GS (including post-chorecystectomy patients) was significantly higher in female patients with RA (15.4%) than in female controls (5.2%, p < 0.01). There was no significant difference in GS incidence between male patients with RA (9.5%) and male controls (3.8%). The percentage of cholesterol stones was 100% in patients with RA with GS but only 66.7% in controls with GS (p < 0.01). Compared to patients with RA without GS, patients with RA with GS were older and had lower C-reactive protein levels, a decreased creatinine clearance and urinary calcium excretion, and an increased incidence of hypercholesterolemia. CONCLUSION: We observed a high incidence of GS in female patients with RA. With our previous observation of a high incidence of renal stones in patients with RA, these results suggest the importance of US as a diagnostic tool in the management of RA.
10451613 [Sweet syndrome associated with articular and renal involvement]. 1999 Apr We report a 29 years old female presenting with fever and painful infiltrated erythematous and violaceous plates with pseudo vesicles in the surface, located in both arms, four days after having suffered a tonsillitis. She was admitted with the diagnosis of Sweet syndrome and the lesions disappeared spontaneously. Two months later, she presented with a similar condition, again after an upper respiratory infection. Five months later, she was admitted with arthralgias with positive rheumatoid factor and antinuclear antibodies. Three years after the first admission, she was admitted with an acute glomerulonephritis and renal failure after another upper respiratory infection. Sweet syndrome was described in 1964 and, although initially considered benign, its association with inflammatory diseases or cancer has been reported.
11750293 The course of depression in recent onset rheumatoid arthritis: the predictive role of disa 2001 Dec BACKGROUND: This study aimed to investigate the course of depression for patients with recently diagnosed rheumatoid arthritis (RA) and to investigate predictors of depression. METHODS: Twenty-two patients with a history of recently diagnosed RA of less than 2 years were assessed on a variety of clinical outcome and process measures on six assessment occasions over a 21-month period. These 22 patients constituted the control group of a controlled trial and received standard outpatient clinic treatment during follow-up. RESULTS: Patients became significantly more depressed over time. A set of five factors were found to consistently predict depression at the following assessment. These were initial level of depression, disability, pain, beliefs about the consequences of arthritis and coping strategies. CONCLUSIONS: The results confirm the importance of psychological factors in early RA and their relative independence from physical findings. This is the first study to document the importance of illness perceptions in recent onset RA.
9287389 Total joint arthroplasty and the immune response. 1997 Aug Total joint replacement arthroplasty has proved highly successful in the management of osteoarthritis and rheumatoid arthritis. The cause of aseptic loosening of prosthetic joint replacement components is unclear. Early experience with total joint arthroplasty was plagued by a number of problems that no longer exist as major impediments to long-term success. Improvement in the operating room environment and the use of prophylactic antibiotics have substantially reduced the high incidence of infection to less than 1%. Implant materials have long been considered biologically inert, but recent studies indicate that inflammatory reactions directed against the implanted materials may contribute to aseptic loosening. Currently, particulate debris from cement or polyethylene causing loosening of the prosthesis is the major problem in total joint arthroplasty. Significant data suggest a progression from a simple inflammatory reaction to complex immune responses against the biomaterials. The cellular responses to particles of polymethylmethacrylate, ultra-high-molecular-weight polyethylene, and alloys of cobalt-chromium and titanium have been assayed in vitro in patients with osteoarthritis, rheumatoid arthritis, and avascular necrosis who had total joint replacement. Elevated immunologic cell proliferation responses to both acrylic and cobalt chromium were observed in patients with aseptically loosened prostheses. These findings suggest that the development of a cellular response to particulate debris may be significant in the pathogenesis of aseptic loosening.
10210086 Arthroscopic resection of the radial head. 1999 Mar The authors describe arthroscopic radial head resection in patients with post-traumatic arthritis after fractures of the radial head or in patients with rheumatoid arthritis of the elbow joint, as an expanded indication for elbow arthroscopy. Arthroscopic radial head resection allows the surgeon to deal with the intrinsic joint pathology, as well as with accompanying symptoms such as synovitis, capsular contracture, or loose bodies. The portals used are the proximal medial, anterolateral, and the midlateral portal. The anterior three quarters of the radial head and 2 to 3 mm of the radial neck are resected with the stone-cutting abrader in the anterolateral portal and the arthroscope in the proximal medial portal. For resection of the posterior portion of the radial head, the abrader may be transferred to the midlateral portal. This permits resection of the remnants of the radial head posteriorly and also at the proximal radioulnar joint. Arthroscopic treatment allows the patient to begin and maintain an aggressive postoperative physical therapy program immediately after surgery, thus decreasing the risk of anterior scarring and reoccurring contracture of the capsule of the elbow joint.
11053099 Role of interleukin 1 and interleukin 1 receptor antagonist in the mediation of rheumatoid 2000 Nov Chronic arthritis is characterised by chronic joint inflammation and concurrent joint erosion and destruction. The inflammatory cytokine interleukin 1 (IL1) has been shown to be a key mediator in the autoimmune disease rheumatoid arthritis (RA). Interleukin 1 mediates bone resorption and cartilage destruction, but may not play as dominant a part in joint swelling and inflammation. Interleukin 1 receptor antagonist (IL1Ra) selectively inhibits the effects of IL1 by competing for the IL1 receptor on all surfaces of the synovium. In a randomised controlled trial in 472 patients with active disease, IL1Ra 30 mg/day, 75 mg/day or 150 mg/day given by subcutaneous injection significantly reduced the signs and symptoms of RA at 24 weeks. An American College of Rheumatology (ACR) 20% response was seen in 43% of the patients treated with 150 mg/day at 24 weeks. IL1Ra was well tolerated; injection site reactions were the most common adverse event. In another trial, in 419 patients with active RA treated concomitantly with methotrexate, there were ACR 20% responses after 24 weeks in 42% of the patients treated with 1 mg/kg/day by subcutaneous injection and in 35% of those treated with 2 mg/kg/day. I1Ra offers a unique selective, targeted mechanism of action to block the IL1 mediated effects of RA.
11132984 A long-term follow-up study of cervical lesions in rheumatoid arthritis. 2000 Dec To determine the natural history of cervical lesions in rheumatoid arthritis, 161 patients who had been followed for a minimum of 5 years were enrolled in this study. The average follow-up period was 10.2 years (range, 5 to 20 years). The severity of the rheumatoid arthritis was classified into three types based on the multiplicity of peripheral joint rheumatoid involvement: a least erosive subset, a more erosive subset, and a mutilating disease subset. Ninety-two patients (57%) had upper cervical involvement, which progressed in the order of anterior atlantoaxial subluxation, anterior atlantoaxial subluxation combined with vertical subluxation, and vertical subluxation alone. Subaxial subluxation was found in 18 patients (11%). In 17 of these 18 patients, upper cervical lesions were also noted. The incidence of cervical involvement in each disease subset was 39% in the least erosive group, 83% in the more erosive group, and 100% in the mutilating disease group. Fifty percent of the patients with cervical involvement had neck pain, and the remaining patients were asymptomatic. Neural involvement occurred in 10 patients. In 7 of these 10 patients, vertical subluxation of the atlas was responsible for the neural deficit. Six patients required surgical intervention because of progressive myelopathy.
9861791 Update on treatment of rheumatoid arthritis. 1998 Nov OBJECTIVE: To review current treatment of rheumatoid arthritis (RA), as well as recent advances. DATA SOURCES: MEDLINE search from 1990 to 1998 for human studies using search terms "rheumatoid arthritis"; "cyclooxygenase inhibitors" combined with "anti-inflammatory agents, nonsteroidal"; "tumor necrosis factor" limited to "antagonists and inhibitors"; "isoxazoles." DATA SYNTHESIS: RA is a chronic inflammatory disease characterized by symmetrical joint involvement, usually of the small joints of the hands and feet. Although the hallmark of the disease is inflammation of joints, other organ systems--including the eyes, blood vessels, lungs, and cardiopulmonary system--may also be involved. Treatment of RA requires both drug and non-drug approaches. Current drug therapy consists of combinations of nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). Corticosteroids are also used either for short-term treatment during initiation of therapy, in bursts during acute disease flares, or chronically in low doses. A number of promising new agents are in development. NSAIDs with preferential inhibition of cyclooxygenase II may offer a better safety profile than existing agents. Leflunomide and biological agents such as etanercept may provide benefit for patients who fail to achieve adequate response from conventional therapy. CONCLUSION: Traditional approaches to treatment of RA include NSAIDs combined with DMARDs. New agents just reaching the market represent important advances and have the potential to make a positive impact on treatment of RA.
11014357 Suppression of arthritis and protection from bone destruction by treatment with TNP-470/AG 2000 Sep OBJECTIVE: We assessed the clinical and histologic features of angiogenesis inhibition in a transgenic mouse model of arthritis that closely resembles rheumatoid arthritis (RA) in humans. METHODS: KRN/NOD mice, which spontaneously develop arthritis, were treated with TNP-470, an angiogenesis inhibitor. Disease was monitored by use of clinical indices and histologic examinations; circulating blood levels of vascular endothelial growth factor were determined by enzyme-linked immunosorbent assay. RESULTS: In the preventive protocol, with TNP-470 administration at a dosage of 60 mg/kg of body weight, the onset of arthritis was delayed and its clinical intensity was rather mild; 100% of placebo-treated transgenic mice developed arthritis that led to severe articular destruction. At a dosage of 90 mg/kg of TNP-470, the appearance of clinical signs was delayed for a longer period of time and disease was almost abolished. The therapeutic regimen alleviated clinical signs only when given during the very early stage of disease. Reductions in cartilage and bone destruction by TNP-470 treatment were observed histologically, a feature that was still evident at 30 and 80 days after injections were withdrawn. CONCLUSION: Our demonstration that in vivo administration of an angiogenesis inhibitor suppresses arthritis and protects from bone destruction provides new insight into the pathogenesis of the disease and opens new possibilities in the treatment of RA in humans.
9711159 Abnormal bone remodelling in inflammatory arthritis. 1998 Aug Osteopenia is responsible for substantial comorbidity in patients suffering from rheumatoid arthritis and is an important factor in the surgical management of joint disease. In animal models of bone loss stimulated by inflammatory arthritis, increased bone remodelling and altered microstructure of bone have been documented. The subchondral bone plate near the joint surface is narrow and perforated by vascular inflammatory invasion, and in the shaft the thin cortices are weakened by giant resorption defects. Biomechanical tests and a mathematical model of bone strength suggest that cortical defects, much larger than those found in normal osteonal remodelling, are principally responsible for the experimentally observed loss of strength. Similarly, these defects may explain the increased femoral fracture risk in rheumatoid arthritis. The osteoclast, the cell resorbing bone, is demonstrated in increased number and activity in rheumatoid arthritis and in animal models. Bisphosphonates, drugs that inhibit osteoclast function, have been shown experimentally to reduce both focal and generalized osteopenia and to prevent loss of bone strength. Bisphosphonates also protect articular cartilage from damage characteristic of inflammatory arthritis. The mechanism of chondroprotection may be prevention of subchondral bone resorption by the osteoclast and also an altered distribution of bone marrow cells. Thus, bisphosphonates, currently in clinical use for other bone metabolic diseases, appear to have potential as prophylaxis and treatment for osteopenia and joint damage in inflammatory arthritis.
10343530 Successful conservative treatment of rheumatoid subaxial subluxation resulting in improvem 1999 Feb OBJECTIVE: To report the efficacy of conservative treatment with cervical traction and immobilisation with a Halo vest, in two consecutive rheumatoid arthritis patients with progressive cervical myelopathy caused by subaxial subluxation. METHODS: Description of neurological symptoms and signs and findings in plain radiography (PR) and magnetic resonance imaging (MRI) of the cervical spine before and after treatment of the subaxial subluxation by traction and immobilisation with a Halo vest during four months. RESULTS: During four months of traction and immobilisation neurological examination showed a considerable improvement of the signs and symptoms of cervical myelopathy. Afterwards PR and MRI of the cervical spine showed reduction of the subaxial subluxation. Eventually firm stabilisation was obtained in both patients without surgery of the cervical spine. CONCLUSION: Cervical traction and immobilisation with a Halo vest can be considered as an independent conservative treatment in rheumatoid arthritis patients with cervical myelopathy caused by subaxial subluxation.
14635282 Adaptations made by rheumatoid arthritis patients to continue working: a pilot study of wo 2000 Apr OBJECTIVES: The goals of this pilot study were to use qualitative research techniques in a group of currently employed patients with rheumatoid arthritis (RA) to develop categories of challenges encountered in maintaining employment and categories of successful adaptations made to continue working; and to identify obstacles considered to be persistent threats to continued employment. METHODS: Patients were interviewed by telephone with a questionnaire composed of structured-response format and open-ended response format questions focusing on specific challenges and adaptations in the workplace. RESULTS: Of the 22 patients interviewed, 96% were women, mean age was 50 years, 84% were college graduates, and the majority had light physical job demands and high autonomy over their work and hours worked. Patients encountered diverse challenges, such as fatigue, pain, typing, writing, physical requirements, maintaining a pleasant disposition, working overtime, traveling for business, commuting, being on time, not being able to choose rest periods, and environmental issues. Patients also made multiple adaptations to continue working, the most helpful being changing job or altering career path (36%), altering work hours (32%), using more disease-modifying antirheumatic drugs (27%), using car service (23%), sleeping more (18%), and working at home (14%). Patients were not at all confident in their ability to continue working because of RA, and perceived the following persistent threats to continued employment: fatigue (45%), not being able to use hands (45%), not being able to choose rest periods (27%), and commuting problems (18%). In addition, patients confronted psychological stresses, such as dealing with coworkers and supervisors and balancing job and personal roles. These challenges and adaptations included unfavorable work-related occurrences, or "negative work-role events." CONCLUSIONS: Seemingly successfully employed patients with RA faced multiple challenges and made major adaptations to maintain employment and still perceived their employment to be in jeopardy because of RA. The findings of this study have important implications for screening patients at risk for negative work-role events and for possible work-related and social support interventions aimed at preserving employment.
9310117 Pure red cell aplasia in a man with RA. 1997 A 65 year-old man with long-standing rheumatoid arthritis (RA) developed pure red cell aplasia (PRCA), which was apparently not caused by drugs or viral infections. The condition responded favorably to danazol in combination with sulfasalazine. This was probably the 2nd case of RA with PRCA in a male patient.
11129366 Structured writing about stressful events: exploring potential psychological mediators of 2000 Nov In a previous study, the authors found that structured writing about stressful events improved symptomatology in 112 patients with rheumatoid arthritis and asthma relative to patients who did not write (J. Smyth, A. Stone, A. Hurewitz, & A. Kaell, 1999). However, little is currently known about the pathways from the intervention to alterations in outcomes. In addition to measuring symptom outcomes after the intervention in the previous study, the authors monitored perceived stress, quality of sleep, affect, substance use, and medication use on a momentary basis for the 7 days prior to writing, during the 3 intervention days, and for the 14 days following the intervention (N = 105). These variables were tested in a secondary data analysis to determine whether they mediated the effects observed in the J. Smyth, A. Stone, et al. study. No evidence was found supporting mediation, and the mechanism underlying structured writing about stressful events remains unknown.
9733446 Forefoot deformity, pain, and mobility in rheumatoid and nonarthritic subjects. 1998 Sep OBJECTIVE: To evaluate how painful metatarsal arthritis affects foot and ankle mechanics and mobility. METHODS: We studied 16 symptomatic forefeet in 10 patients with rheumatoid arthritis (RA) and compared them with 14 asymptomatic forefeet in 7 nonarthritic subjects. RA limbs with significant disease at other locations were excluded. We measured pain and deformity of the foot using a visual analog scale and a modified articular index. A video based 3 dimensional gait analysis system and force platform were used to collect data on subjects walking barefoot at a self-selected pace according to an established protocol. Mobility level was quantified using the Sickness Impact Profile (SIP) ambulation subscale. RESULTS: We observed considerable pain and deformity of the forefeet of RA subjects. During gait, motion and force measures revealed that RA subjects significantly (p < 0.005) delayed and reduced forefoot loading, which minimized use of the foot as a rigid level for push off. As a result, stride lengths were shorter and gait was slower compared to nonarthritic subjects. SIP scores revealed that these changes in gait resulted in moderate disability in RA subjects (p=0.05). CONCLUSION: Impairments of the forefoot due to RA include pain and deformity, which produce characteristic stance phase abnormalities in foot function, a slow walking speed, and moderate disability.